During the past four years of support we have made tremendous progress, have achieved the goals o[unreadable] the original proposal and have been able to go far beyond the proposed aims. Among these achievements[unreadable] we were able to develop a mouse model of CLL, to establish the role of the Tcl1/Akt pathway in the[unreadable] pathogenesis of CLL, to discover the role of miR genes in CLL, to dissect the genetics of 6q alterations in[unreadable] CLL with poor prognosis, to discover the ARLTS1 tumor suppressor gene at 13q14 and a germline mutation[unreadable] of this gene that predisposes to a variety of human cancers including CLL, and to develop a miR gene chip[unreadable] to investigate patterns of miR expression in this malignancy.[unreadable] In this renewal application we propose:[unreadable] 1) to continue our studies to dissect the genetics of sporadic and familial CLL;[unreadable] 2) to establish the role of miR genes in sporadic and familial CLL.